Health and Medicine

Taste tests, etc.

Only the sperm knows

Why is a sperm like a nose? Because both can, in a sense,
"smell," says Hopkins MD/PhD student Loren Walensky. He finds
that sperm tails contain the same types of odor-binding proteins
that noses do. The proteins, he suggests, "smell" odor messages
from the egg, which allow the sperm to find the egg.

The finding could explain a lot about the awesome
interaction of sperm meets egg. Like a tiny tadpole swimming
across a murky pond in search of a speck of food, a minute sperm
must blindly swim an immense distance. Sperm awaiting the
appearance of an egg can remain tucked in the vaginal lining for
days, says Walensky. "Upon ovulation, the sperm immediately
bolts, and reaches the fertilization site within minutes," he
says. How does the sperm know where to go?

Scientists theorize that the sperm navigates toward some
chemical signal emitted by the egg, a reaction they call
chemotaxis. But precise details are vague. In 1992, investigators
at the University of Brussels spotted proteins in dog testicles
like those found in odor receptors. Those results started
scientists thinking that the tracking mechanism used by sperm
could be similar to the pathway for smell. In the nose, airborne
odor molecules, say from a pepperoni pizza, appear to bind to
receptor molecules, and trigger a chain reaction that eventually
tells the brain there is pepperoni nearby.

Intrigued by the finding of the Brussels group, Walensky
decided to search for similar receptors in sperm. In experiments
reported in the January Molecular Medicine, he used antibodies to
odorant receptor proteins developed in the lab of Hopkins
neuroscientist Gabriele Ronnett. The antibodies, he reports, bind
to proteins in the upper tail regions of rat sperm--the regions
that contain clumps of mitochondria, the powerhouses that fuel
cellular activities like swimming. So the receptors could act
much the way they do in the nose; they could be transmitting
messages from the egg to regions of the sperm responsible for
steering it to the egg, suggests Walensky.

Sperm may also have a way to tone down the reaction, posits
Walensky. Such "desensitization" occurs in the nose, as when you
stop smelling garlic after an hour in an Italian restaurant.
Likewise, Walensky discovered that sperm appear to contain a
second set of proteins that tone down the first set of receptors.
These proteins might go to work when the sperm finally reaches
the egg, telling it to stop swimming and start fertilizing, he
says.

"Perhaps," he speculates, "evolution put the receptors on
the tail." Since only a small percentage of sperm in ejaculate
succeeds in getting close to the egg, and only one ultimately
finishes the race, sniffing out the egg could be nature's test
for the most robust sperm. Further research could lead to new
methods of contraception, says Walensky. For example, by finding
a way to inhibit the sperm's odor receptor proteins, scientists
might devise a way to prevent fertilization. Conversely, a
technique that enhances the sperm's egg-sniffing ability could
help aid reproductive technology such as in vitro fertilization.
--MH

Timing of immune response affects
development of AIDS

Just as some people infected with HIV remain healthy for well
over a decade, some progress to full-blown AIDS in less than
three years. Why the difference?

Immune response to highly specific parts of the virus in the
first few months after infection may be key, says Homayoon
Farzadegan, an epidemiologist at the School of Public Health. In
a recent study, 17 gay men developed AIDS within three years
after producing few antibodies to HIV gag-gene products when
newly infected. However, 43 men who initially showed strong
immune response to gag-gene products remained symptom-free for at
least six years.

The findings could help physicians identify which patients
may need treatment soon, and which patients probably will not
develop symptoms for many years, says Farzadegan. As well,
treatments might be developed to target key immune defenses.
--EH

Painkillers associated with some kidney
failure

People who take one or more Tylenol tablets daily (or other
products containing the pain reliever acetaminophen) could double
their risk of kidney failure, according to a study by Hopkins
epidemiologists.

"Acetaminophen could be responsible for about 10 percent of
kidney failure that we see in this [mid-Atlantic] region," says
Paul Whelton, director of the School of Public Health's Welch
Center for Prevention, Epidemiology, and Clinical Research.
People in kidney failure, or end-stage renal disease, generally
require dialysis. If heavy users of acetaminophen reduced or
stopped taking the drug, says Whelton, it could reduce the number
of people needing dialysis by 10 percent.

The investigators caution, however, that kidney failure is
relatively rare, occurring in fewer than two out of every 10,000
people each year. "So even doubling that number is still not a
high risk," says Whelton. He also emphasizes that "the results
have primary relevance for relatively heavy users of the drug,
those who consume on average more than one pill a day. I don't
believe the intermittent user should be concerned."

The investigators surveyed 716 dialysis patients about their
use of acetaminophen, aspirin, and non-steroidal anti-
inflammatory drugs. They compared those results to the drug use
of 361 healthy people. All of those surveyed were from the mid-
Atlantic states.

Kidney failure rose in a dose-dependent fashion, the
scientists report in the December 22, 1994, New England Journal
of Medicine. People who took acetaminophen between two and seven
times a week had a 1.4 times greater risk than normal. People who
took the drug one or more times a day had a 2.1 times greater
risk.

The study also showed that people who used relatively large
amounts of nonsteroidal anti-inflammatory drugs, such as
ibuprofen, naproxen, or indomethacin also appeared to increase
their risk of kidney failure. Aspirin, however, did not appear to
increase the chances of kidney damage.

"We need additional research to be sure this is a truly
causal relationship," says Whelton. Until then, he advises people
to use "good common sense. Do not use medications unless there's
a reason. If you use a lot of pain reliever, consult with a
doctor." People who need a lot of pain medication or those at
risk of kidney failure might want to use aspirin, he says.
--MH

Battling anemia in Sri
Lanka

In Sri Lanka, hundreds of residents are taking an unusual taste
test. They're sampling a variety of local breads and bread
products to see whether they can detect anything unusual in any
of the items. Do the testers notice a flavor of rusty nails in a
sample of flat bread, for instance? Do they smell anything
peculiar in a particular cookie?

Though the test may seem like a challenge for epicures, its
ultimate goal is to conquer anemia among Sri Lanka's 18 million
residents. Estimates indicate that half the women in Sri Lanka
and throughout Southeast Asia have the disorder, the most common
nutritional disorder in the world, says Rebecca Stoltzfus,
assistant professor of nutrition at the School of Public Health.
"Southeast Asia is probably the worst area in the world for iron
deficiency," she says.

Anemia lowers a person's ability to think, decreases
productivity, and increases the risk of infection. Pregnant women
with anemia have a greater risk of dying in pregnancy or
childbirth. In children, anemia can retard growth and mental
development. "As countries develop and get rid of other
nutritional problems, anemia hangs on," says Stoltzfus,
particularly in places where people consume few animal products,
which supply iron. Parasites like hookworm also contribute to
anemia by eating blood, which stores most of the body's iron.

With the United States Agency for International Development
and the Sri Lankan government, Stoltzfus is developing a program
to reduce anemia by fortifying all Sri Lanka's wheat flour with
iron. Step one are the taste tests, to see whether volunteers can
taste or smell iron in various breads, pastas, crackers, and
cookies prepared with iron-fortified flour.

"Food fortification is a good intervention," says Stoltzfus.
"It's extremely inexpensive. The cost-benefit analysis becomes
meaningless." Furthermore, wheat is a prime food to fortify in
Sri Lanka, she says, since it comprises about 40 percent of the
nation's staple calories. All the country's wheat is imported
from the U.S. and processed at one mill. Adding iron to the
nation's wheat would be relatively simple.

So why hasn't it been done already? One stumbling block is
that scientists first need to find out how much iron and what
type of iron should be used. "We'd like to pack in as much iron
as we can without it tasting like rust," says Stoltzfus. Bread
with too much iron won't be palatable, and consumers won't buy
it. So the products in the taste test contain varying amounts.

The bread products also contain five different forms of
iron, ranging from ones that are highly bioavailable (more likely
to be absorbed by the blood supply) to those that are of low
bioavailability (thus more likely to be excreted). Ideally, says
Stolzfus, "we'd like to pick the highest level of bioavail-
ability. But when you use iron that is more bioavailable it can
react with the fats in the bread," she says. "The bread ends up
tasting like nails, or the color changes to green, or the bread
doesn't rise as well."

For phase two of the project, Stoltzfus and her colleagues
are designing a study to monitor the levels of hemoglobin (the
iron-carrying molecule found in red blood cells) and rates of
anemia in people who are eating fortified flour. The study seeks
to make sure that fortification really does increase their blood
iron levels.--MH

Whipple at Hopkins is safer and
cheaper

Health insurance companies often steer patients requiring
specialty care to hospitals they think provide the cheapest
service. But those companies may be doing themselves a
disservice, says a team of Hopkins investigators. Academic
medical centers can be more successful and less costly, at least
for a complicated, risky operation for pancreatic cancer known as
the Whipple procedure, they report.

The scientists found that 2.2 percent of inpatients for the
procedure died at Hopkins as compared to an average of 13.5
percent at 38 other hospitals surveyed. Further, the cost of the
procedure at Hopkins was $26,204 as com- pared to $31,659 at the
other hospitals. The authors of the study, which appeared in the
January Annals of Internal Medicine, surveyed the records of all
patients who underwent the Whipple procedure in Maryland from
1988 through the first half of 1993. Hopkins performed half of
the total 501 procedures during that time, and 38 lower volume
hospitals performed the rest.

More practice--on the part of the surgeons, nurses in the
operating room, and staff on the hospital floors--accounts for
part of the higher success rate, says Toby Gordon, vice president
for planning and marketing at Hopkins Hospital, who conducted the
study with director of surgery John Cameron and others. A more
experienced team of people reduces complications like infections
that can follow the Whipple procedure. Also, experienced staff
order fewer lab tests and radiological services, and their
patients are less likely to need long stays in intensive care,
says Gordon. At Hopkins, patients spent an average of two days in
the ICU following the Whipple procedure, as compared to four days
for patients at the other 38 hospitals. "Gains in efficiency
allow us to save costs for the patient," says Gordon.
--MH

Drug helps prevent sickle cell
crises

A Hopkins-led national study has revealed the first drug that
helps stave off the excruciatingly painful attacks of sickle cell
disease. The data are so clear that officials stopped the
clinical trial in January, four months before the study was
scheduled to end, and asked that volunteers who had been
receiving placebo be given the medication. The drug, hydroxyurea,
cuts in half the number of painful episodes in sickle cell anemia
patients.

Sickle cell disease, which afflicts about 150 out of every
100,000 African Americans, stems from a defect in hemoglobin, the
oxygen-carrying molecule of red blood cells. In people with the
disease, hemoglobin molecules can clump into rigid polymers,
causing the red blood cells to stiffen into sickles that stick
together and clog blood vessels, which prevents oxygen from
reaching organs. Results include infections, strokes, blindness,
and a life-threatening condition called acute chest syndrome
involving severe chest pain and fever. Sickle cell patients have
equated attacks of the disease with the pain of childbirth. On
average, people with the disease die in their 40s.

Until now, the best help for sickle cell anemia patients was
pain relief through painkiller drugs or blood transfusions.
Hydroxyurea is the first drug that actually prevents some of the
painful attacks.

Scientists propose that the drug triggers the production of
fetal hemoglobin, a form normally produced only in the fetus and
newborn. Fetal hemoglobin may not cause cell sickling in patients
with sickle cell disease.

Hopkins professor of medicine Samuel Charache notes,
however, that hydroxyurea is not a cure. To continue to reap its
benefits, patients need to take the medication daily. He also
says that hydroxyurea should not be offered to children or to
pregnant women until further studies are conducted. The drug also
has the potential to cause a drastic and potentially fatal
reduction in blood cells.

Charache and Michael Terrin, vice president of the Maryland
Medical Research Institute in Baltimore, led the investigation,
which followed 299 adult patients at 21 clinical centers around
the United States. Half the patients took daily doses of
hydroxyurea and half took placebo capsules. Those taking
hydroxyurea were seen at hospitals for crises half as often as
patients taking placebo, and also required fewer blood
transfusions. --MH

Screening for suicide

Each year, about 30,000 Americans kill themselves, and most have
seen their physicians during the previous year, says Lisa Cooper-
Patrick, a Hopkins specialist in internal medicine. Typically,
these patients complain about stress-related physical ailments:
headaches, trouble sleeping, feeling vaguely terrible.

But only some of them seem depressed, so their doctors don't
tend to ask about suicidal thoughts. In most cases, the risk of
suicide is missed.

Now, using more than 6,000 interviews from a massive earlier
study by the National Institute of Mental Health, Cooper-Patrick
and colleagues have isolated traits shared by many people with
suicidal thoughts: sleep disturbance, intense guilt, depressed
mood, and feelings of hopelessness. More than 90 percent of those
who expressed feelings of either worthlessness or despair also
had suicidal ideation, says Cooper-Patrick.

The team suggests that doctors should routinely inquire
about these four symptoms, then probe for suicidal thoughts if
they get even one positive answer. Such screening, the study
found, would identify 84 percent of patients who are thinking
about suicide.

People can then be referred for help, to prevent the
downward slide from suicidal "ideation" to contemplation,
threats, attempts, and finally completion. "If you only ask
patients who have already been diagnosed with psychiatric
disorders," says Cooper-Patrick, "you'll miss two-thirds of the
ones who are thinking about suicide."

The data draw from 6,041 adults who were interviewed as part
of an NIMH study to assess rates of psychiatric illness in the
general population. All had told trained interviewers that they
had received care in a general medical setting within the
previous year, and all said that at some time within the last
year they had felt so low they thought of committing suicide.

To screen general medical patients, Cooper-Patrick advises
beginning with the least threatening question: "Have you ever had
a period of two weeks or more when you had trouble falling
asleep, staying asleep, waking up too early, or sleeping too
much?" Of general medical patients, 18 percent will say yes. Of
suicidal patients, two-thirds will say yes.

The study was published in December 1994 in the Journal of
the American Medical Association. --EH